tbuckley/cabot-search huggingface dataset:
Transcriptional control of nucleus accumbens neuronal excitability by retinoid X receptor alpha tunes sensitivity to drug rewards
Authors: Arthur Godino, Marine Salery, Romain Durand-de Cuttoli, Molly S. Estill, Leanne M. Holt, Rita Futamura, Caleb J. Browne, Philipp Mews, Peter J. Hamilton, Rachael L. Neve, Li Shen, Scott J. Russo, Eric J. Nestler
Journal: Neuron (2023)
Skin-interfaced electronics: A promising and intelligent paradigm for personalized healthcare
Authors: Yangzhi Zhu, Jinghang Li, Jinjoo Kim, Shaopei Li, Yichao Zhao, Jamal Bahari, Payam Eliahoo, Guanghui Li, Satoru Kawakita, Reihaneh Haghniaz, Xiaoxiang Gao, Natashya Falcone, Menekse Ermis, Heemin Kang, Hao Liu, HanJun Kim, Tanveer Tabish, Haidong Yu, Bingbing Li, Mohsen Akbari, Sam Emaminejad, Ali Khademhosseini
Journal: Biomaterials (2023)
Molnupiravir and risk of hospital admission or death in adults with covid-19: emulation of a randomized target trial using electronic health records
Authors: Yan Xie, Benjamin Bowe, Ziyad Al-Aly
Journal: BMJ (2023)

To emulate a randomized target trial to estimate the association between the antiviral drug molnupiravir and hospital admission or death in adults with SARS-CoV-2 infection in the community during the omicron predominant era who were at high risk of progression to severe covid-19. Emulation of a randomized target trial using electronic health records. US Department of Veterans Affairs. 85 998 adults with SARS-CoV-2 infection between 5 January and 30 September 2022 and at least one risk factor for progression to severe covid-19: 7818 participants were eligible for and treated with molnupiravir and 78 180 received no treatment. The primary outcome was a composite of hospital admission or death at 30 days. The clone method with inverse probability of censoring weighting was used to adjust for informative censoring and balance baseline characteristics between the groups. The cumulative incidence function was used to estimate the relative risk and the absolute risk reduction at 30 days. Molnupiravir was associated with a reduction in hospital admissions or death at 30 days (relative risk 0.72 (95% confidence interval 0.64 to 0.79)) compared with no treatment; the event rates for hospital admission or death at 30 days were 2.7% (95% confidence interval 2.5% to 3.0%) for molnupiravir and 3.8% (3.7% to 3.9%) for no treatment; the absolute risk reduction was 1.1% (95% confidence interval 0.8% to 1.4%). Molnupiravir appeared to be effective in those who had not been vaccinated against covid-19 (relative risk 0.83 (0.70 to 0.97) and absolute risk reduction 0.9% (0.2% to 1.9%)), had received one or two vaccine doses (0.69 (0.56 to 0.83) and 1.3% (0.7% to 1.9%)), and had received a booster dose (0.71 (0.58 to 0.83) and 1.0% (0.5% to 1.4%)); in those infected during the era when the omicron subvariant BA.1 or BA.2 was predominant (0.72 (0.62 to 0.83) and 1.2% (0.7% to 1.6%)) and when BA.5 was predominant (0.75 (0.66 to 0.86) and 0.9% (0.5% to 1.3%)); and in those with no history of SARS-CoV-2 infection (0.72 (0.64 to 0.81) and 1.1% (0.8% to 1.4%)) and with a history of SARS-CoV-2 infection (0.75 (0.58 to 0.97) and 1.1% (0.1% to 1.8%)). The findings of this emulation of a randomized target trial suggest that molnupiravir might have reduced hospital admission or death at 30 days in adults with SARS-CoV-2 infection in the community during the recent omicron predominant era who were at high risk of progression to severe covid-19 and eligible for treatment with molnupiravir.
Response to 'Hyperbaric oxygen facilitates teniposide-induced cGAS-STING activation to enhance the antitumor efficacy of PD-1 antibody in HCC' by Yang<i>et al</i>
Authors: Kun Li, Yunfei Qin, Linsen Ye
Journal: Journal for ImmunoTherapy of Cancer (2023)

We are very grateful to the authors for their letter in which they present some suggestions regarding the establishment of a mouse hepatocellular carcinoma (HCC) tumor model.[1][1] We believe that these new insights are valuable and worthy of careful consideration by many researchers. The letter
Interaction between tumor cell TNFR2 and monocyte membrane-bound TNF-α triggers tumorigenic inflammation in neuroblastoma
Authors: Julie A Tomolonis, Xin Xu, Kshiti H Dholakia, Chunchao Zhang, Linjie Guo, Amy N Courtney, Siyue Wang, Julien Balzeau, Gabriel A Barragán, Gengwen Tian, Erica J Di Pierro, Leonid S Metelitsa
Journal: Journal for ImmunoTherapy of Cancer (2023)

Tumor progression and resistance to therapy in children with neuroblastoma (NB), a common childhood cancer, are often associated with infiltration of monocytes and macrophages that produce inflammatory cytokines. However, the mechanism by which tumor-supportive inflammation is initiated and propagated remains unknown. Here, we describe a novel protumorigenic circuit between NB cells and monocytes that is triggered and sustained by tumor necrosis factor alpha (TNF-α). We used NB knockouts (KOs) of TNF-α and TNFRSF1A mRNA (TNFR1)/TNFRSF1B mRNA (TNFR2) and TNF-α protease inbitor (TAPI), a drug that modulates TNF-α isoform expression, to assess the role of each component in monocyte-associated protumorigenic inflammation. Additionally, we employed NB-monocyte cocultures and treated these with clinical-grade etanercept, an Fc-TNFR2 fusion protein, to neutralize signaling by both membrane-bound (m) and soluble (s)TNF-α isoforms. Further, we treated NOD/SCID/IL2Rγ(null) mice carrying subcutaneous NB/human monocyte xenografts with etanercept and evaluated the impact on tumor growth and angiogenesis. Gene set enrichment analysis (GSEA) was used to determine whether TNF-α signaling correlates with clinical outcomes in patients with NB. We found that NB expression of TNFR2 and monocyte membrane-bound tumor necrosis factor alpha is required for monocyte activation and interleukin (IL)-6 production, while NB TNFR1 and monocyte soluble TNF-α are required for NB nuclear factor kappa B subunit 1 (NF-κB) activation. Treatment of NB-monocyte cocultures with clinical-grade etanercept completely abrogated release of IL-6, granulocyte colony-stimulating factor (G-CSF), IL-1α, and IL-1β and eliminated monocyte-induced enhancement of NB cell proliferation in vitro. Furthermore, etanercept treatment inhibited tumor growth, ablated tumor angiogenesis, and suppressed oncogenic signaling in mice with subcutaneous NB/human monocyte xenografts. Finally, GSEA revealed significant enrichment for TNF-α signaling in patients with NB that relapsed. We have described a novel mechanism of tumor-promoting inflammation in NB that is strongly associated with patient outcome and could be targeted with therapy.
Evaluation of tumor antigen-specific antibody responses in patients with metastatic triple negative breast cancer treated with cyclophosphamide and pembrolizumab
Authors: Eric D Routh, Mark G Woodcock, Wolfgang Beckabir, Steven P Vensko, Jonathan S Serody, Benjamin G Vincent
Journal: Journal for ImmunoTherapy of Cancer (2023)

The role of B cells in antitumor immunity is becoming increasingly appreciated, as B cell populations have been associated with response to immune checkpoint blockade (ICB) in patients with breast cancer and murine models of breast cancer. Deeper understanding of antibody responses to tumor antigens is needed to clarify the function of B cells in determining response to immunotherapy. We evaluated tumor antigen-specific antibody responses in patients with metastatic triple negative breast cancer treated with pembrolizumab following low-dose cyclophosphamide therapy using computational linear epitope prediction and custom peptide microarrays. We found that a minority of predicted linear epitopes were associated with antibody signal, and signal was associated with both neoepitopes and self-peptides. No association was observed between signal presence and subcellular localization or RNA expression of parent proteins. Patient-specific patterns of antibody signal boostability were observed that were independent of clinical response. Intriguingly, measures of cumulative antibody signal intensity relative to immunotherapy treatment showed that the one complete responder in the trial had the greatest increase in total antibody signal, which supports a potential association between ICB-dependent antibody boosting and clinical response. The antibody boost in the complete responder was largely driven by increased levels of IgG specific to a sequence of N-terminal residues in native Epidermal Growth Factor Receptor Pathway Substrate 8 (EPS8) protein, a known oncogene in several cancer types including breast cancer. Structural protein prediction showed that the targeted epitope of EPS8 was in a region of the protein with mixed linear/helical structure, and that this region was solvent-exposed and not predicted to bind to interacting macromolecules. This study highlights the potential importance of the humoral immune response targeting neoepitopes as well as self epitopes in shaping clinical response to immunotherapy.
More questions than answers to the diagnosis and management of cauda equina syndrome—authors’ reply
Authors: Julie Woodfield, Ingrid Hoeritzauer, Aimun A.B. Jamjoom, Simon Lammy, Savva Pronin, Cathal J. Hannan, Anna Watts, Laura Hughes, Richard D.C. Moon, Holly Roy, Michael T.C. Poon, Paul Thorpe, Nisaharan Srikandarajah, Andreas K. Demetriades, Niall Eames, Philip J. Sell, Patrick F.X. Statham
Journal: The Lancet Regional Health - Europe (2023)
Recent advances in the plant epitranscriptome
Authors: Lisha Shen, Jinqi Ma, Ping Li, Yujin Wu, Hao Yu
Journal: Genome biology (2023)

Abstract Chemical modifications of RNAs, known as the epitranscriptome, are emerging as widespread regulatory mechanisms underlying gene regulation. The field of epitranscriptomics advances recently due to improved transcriptome-wide sequencing strategies for mapping RNA modifications and intensive characterization of writers, erasers, and readers that deposit, remove, and recognize RNA modifications, respectively. Herein, we review recent advances in characterizing plant epitranscriptome and its regulatory mechanisms in post-transcriptional gene regulation and diverse physiological processes, with main emphasis on N 6 -methyladenosine (m 6 A) and 5-methylcytosine (m 5 C). We also discuss the potential and challenges for utilization of epitranscriptome editing in crop improvement.
Multi-ancestry phenome-wide association of complement component 4 variation with psychiatric and brain phenotypes in youth
Authors: Leanna M. Hernandez, Minsoo Kim, Pan Zhang, Richard A. I. Bethlehem, Gil Hoftman, Robert Loughnan, Diana Smith, Susan Y. Bookheimer, Chun Chieh Fan, Carrie E. Bearden, Wesley K. Thompson, Michael J. Gandal
Journal: Genome biology (2023)

Abstract Background Increased expression of the complement component 4A ( C4A ) gene is associated with a greater lifetime risk of schizophrenia. In the brain, C4A is involved in synaptic pruning; yet, it remains unclear the extent to which upregulation of C4A alters brain development or is associated with the risk for psychotic symptoms in childhood. Here, we perform a multi-ancestry phenome-wide association study in 7789 children aged 9–12 years to examine the relationship between genetically regulated expression (GREx) of C4A , childhood brain structure, cognition, and psychiatric symptoms. Results While C4A GREx is not related to childhood psychotic experiences, cognition, or global measures of brain structure, it is associated with a localized reduction in regional surface area (SA) of the entorhinal cortex. Furthermore, we show that reduced entorhinal cortex SA at 9–10 years predicts a greater number and severity of psychosis-like events at 1-year and 2-year follow-up time points. We also demonstrate that the effects of C4A on the entorhinal cortex are independent of genome-wide polygenic risk for schizophrenia. Conclusions Our results suggest neurodevelopmental effects of C4A on childhood medial temporal lobe structure, which may serve as a biomarker for schizophrenia risk prior to symptom onset.
Deficits in mitochondrial TCA cycle and OXPHOS precede rod photoreceptor degeneration during chronic HIF activation
Authors: Vyara Todorova, Mia Fee Stauffacher, Luca Ravotto, Sarah Nötzli, Duygu Karademir, Lynn J. A. Ebner, Cornelia Imsand, Luca Merolla, Stefanie M. Hauck, Marijana Samardzija, Aiman S. Saab, L. Felipe Barros, Bruno Weber, Christian Grimm
Journal: Molecular Neurodegeneration (2023)

Abstract Background Major retinal degenerative diseases, including age-related macular degeneration, diabetic retinopathy and retinal detachment, are associated with a local decrease in oxygen availability causing the formation of hypoxic areas affecting the photoreceptor (PR) cells. Here, we addressed the underlying pathological mechanisms of PR degeneration by focusing on energy metabolism during chronic activation of hypoxia-inducible factors (HIFs) in rod PR. Methods We used two-photon laser scanning microscopy (TPLSM) of genetically encoded biosensors delivered by adeno-associated viruses (AAV) to determine lactate and glucose dynamics in PR and inner retinal cells. Retinal layer-specific proteomics, in situ enzymatic assays and immunofluorescence studies were used to analyse mitochondrial metabolism in rod PRs during chronic HIF activation. Results PRs exhibited remarkably higher glycolytic flux through the hexokinases than neurons of the inner retina. Chronic HIF activation in rods did not cause overt change in glucose dynamics but an increase in lactate production nonetheless. Furthermore, dysregulation of the oxidative phosphorylation pathway (OXPHOS) and tricarboxylic acid (TCA) cycle in rods with an activated hypoxic response decelerated cellular anabolism causing shortening of rod photoreceptor outer segments (OS) before onset of cell degeneration. Interestingly, rods with deficient OXPHOS but an intact TCA cycle did not exhibit these early signs of anabolic dysregulation and showed a slower course of degeneration. Conclusion Together, these data indicate an exceeding high glycolytic flux in rods and highlight the importance of mitochondrial metabolism and especially of the TCA cycle for PR survival in conditions of increased HIF activity.
Cuproptosis: mechanisms and links with cancers
Authors: Jiaming Xie, Yannan Yang, Yibo Gao, Jie He
Journal: Molecular Cancer (2023)

Abstract Cuproptosis was a copper-dependent and unique kind of cell death that was separate from existing other forms of cell death. The last decade has witnessed a considerable increase in investigations of programmed cell death, and whether copper induced cell death was an independent form of cell death has long been argued until mechanism of cuproptosis has been revealed. After that, increasing number of researchers attempted to identify the relationship between cuproptosis and the process of cancer. Thus, in this review, we systematically detailed the systemic and cellular metabolic processes of copper and the copper-related tumor signaling pathways. Moreover, we not only focus on the discovery process of cuproptosis and its mechanism, but also outline the association between cuproptosis and cancers. Finally, we further highlight the possible therapeutic direction of employing copper ion ionophores with cuproptosis-inducing functions in combination with small molecule drugs for targeted therapy to treat specific cancers.
Daratumumab, carfilzomib, and dexamethasone in relapsed or refractory myeloma: final analysis of PLEIADES and EQUULEUS
Authors: Philippe Moreau, Ajai Chari, Albert Oriol, Joaquin Martinez-Lopez, Mathias Haenel, Cyrille Touzeau, Sikander Ailawadhi, Britta Besemer, Javier de la Rubia Comos, Cristina Encinas, Maria-Victoria Mateos, Hans Salwender, Paula Rodriguez-Otero, Cyrille Hulin, Lionel Karlin, Anna Sureda Balari, Joan Bargay, Lotfi Benboubker, Laura Rosiñol, Stefano Tarantolo, Howard Terebelo, Shiyi Yang, Jianping Wang, Ivo Nnane, Ming Qi, Michele Kosh, Maria Delioukina, Hartmut Goldschmidt
Journal: Blood Cancer Journal (2023)
Impact on clinical outcome of follow-up blood cultures and risk factors for persistent bacteraemia in patients with gram-negative bloodstream infections: a systematic review with meta-analysis
Authors: Milo Gatti, Cecilia Bonazzetti, Beatrice Tazza, Renato Pascale, Beatrice Miani, Marta Malosso, Giacomo Beci, Domenico Marzolla, Matteo Rinaldi, Pierluigi Viale, Maddalena Giannella
Journal: Clinical Microbiology and Infection (2023)
Engineering In vitro Models: Bioprinting of Organoids with Artificial Intelligence
Authors: Hyungseok Lee
Journal: Cyborg and Bionic Systems (2023)

In the last decade, organoids have gained popularity for developing mini-organs to support advancements in the study of organogenesis, disease modeling, and drug screening and, subsequently, in the development of new therapies. To date, such cultures have been used to replicate the composition and functionality of organs such as the kidney, liver, brain, and pancreas. However, depending on the experimenter, the culture environment and cell conditions may slightly vary, resulting in different organoids; this factor significantly affects their application in new drug development, especially during quantification. Standardization in this context can be achieved using bioprinting technology-an advanced technology that can print various cells and biomaterials at desired locations. This technology offers numerous advantages, including the manufacturing of complex three-dimensional biological structures. Therefore, in addition to the standardization of organoids, bioprinting technology in organoid engineering can facilitate automation in the fabrication process as well as a closer mimicry of native organs. Further, artificial intelligence (AI) has currently emerged as an effective tool to monitor and control the quality of final developed objects. Thus, organoids, bioprinting technology, and AI can be combined to obtain high-quality in vitro models for multiple applications.
Magnetic Microrobots with Folate Targeting for Drug Delivery
Authors: Min Ye, Yan Zhou, Hongyu Zhao, Xiaopu Wang
Journal: Cyborg and Bionic Systems (2023)

Untethered microrobots can be used for cargo delivery (e.g., drug molecules, stem cells, and genes) targeting designated areas. However, it is not enough to just reach the lesion site, as some drugs can only play the best therapeutic effect within the cells. To this end, folic acid (FA) was introduced into microrobots in this work as a key to mediate endocytosis of drugs into cells. The microrobots here were fabricated with biodegradable gelatin methacryloyl (GelMA) and modified with magnetic metal–organic framework (MOF). The porous structure of MOF and the hydrogel network of polymerized GelMA were used for the loading of enough FA and anticancer drug doxorubicin (DOX) respectively. Utilizing the magnetic property of magnetic MOF, these microrobots can gather around the lesion site with the navigation of magnetic fields. The combination effects of FA targeting and magnetic navigation substantially improve the anticancer efficiency of these microrobots. The result shows that the cancer cells inhibition rate of microrobots with FA can be up to 93%, while that of the ones without FA was only 78%. The introduction of FA is a useful method to improve the drug transportation ability of microrobots, providing a meaningful reference for further research.
The epigenetic regulatory mechanism of PIWI/piRNAs in human cancers
Authors: Qun Zhang, Yazhi Zhu, Xinyu Cao, Wenhui Tan, Jianglong Yu, Yaqiong Lu, Ran Kang, Xiaolan Wang, Ermao Li
Journal: Molecular Cancer (2023)

Abstract PIWI proteins have a strong correlation with PIWI-interacting RNAs (piRNAs), which are significant in development and reproduction of organisms. Recently, emerging evidences have indicated that apart from the reproductive function, PIWI/piRNAs with abnormal expression, also involve greatly in varieties of human cancers. Moreover, human PIWI proteins are usually expressed only in germ cells and hardly in somatic cells, so the abnormal expression of PIWI proteins in different types of cancer offer a promising opportunity for precision medicine. In this review, we discussed current researches about the biogenesis of piRNA, its epigenetic regulatory mechanisms in human cancers, such as N6-methyladenosine (m 6 A) methylation, histone modifications, DNA methylation and RNA interference, providing novel insights into the markers for clinical diagnosis, treatment and prognosis in human cancers.
Plant-derived nanovesicles: Further exploration of biomedical function and application potential
Authors: Aixue Li, Dan Li, Yongwei Gu, Rongmei Liu, Xiaomeng Tang, Yunan Zhao, Fu Qi, Jifu Wei, Jiyong Liu
Journal: Acta Pharmaceutica Sinica B (2023)

Extracellular vesicles (EVs) are phospholipid bilayer vesicles actively secreted by cells, that contain a variety of functional nucleic acids, proteins, and lipids, and are important mediums of intercellular communication. Based on their natural properties, EVs can not only retain the pharmacological effects of their source cells but also serve as natural delivery carriers. Among them, plant-derived nanovesicles (PNVs) are characterized as natural disease therapeutics with many advantages such as simplicity, safety, eco-friendliness, low cost, and low toxicity due to their abundant resources, large yield, and low risk of immunogenicity in vivo. This review systematically introduces the biogenesis, isolation methods, physical characterization, and components of PNVs, and describes their administration and cellular uptake as therapeutic agents. We highlight the therapeutic potential of PNVs as therapeutic agents and drug delivery carriers, including anti-inflammatory, anticancer, wound healing, regeneration, and antiaging properties as well as their potential use in the treatment of liver disease and COVID-19. Finally, the toxicity and immunogenicity, the current clinical application, and the possible challenges in the future development of PNVs were analyzed. We expect the functions of PNVs to be further explored to promote clinical translation, thereby facilitating the development of a new framework for the treatment of human diseases.
Time-Varying Functional Connectivity of Rat Brain during Bipedal Walking on Unexpected Terrain
Authors: Honghao Liu, Bo Li, Pengcheng Xi, Yafei Liu, Fenggang Li, Yiran Lang, Rongyu Tang, Nan Ma, Jiping He
Journal: Cyborg and Bionic Systems (2023)

The cerebral cortex plays an important role in human and other animal adaptation to unpredictable terrain changes, but little was known about the functional network among the cortical areas during this process. To address the question, we trained 6 rats with blocked vision to walk bipedally on a treadmill with a random uneven area. Whole-brain electroencephalography signals were recorded by 32-channel implanted electrodes. Afterward, we scan the signals from all rats using time windows and quantify the functional connectivity within each window using the phase-lag index. Finally, machine learning algorithms were used to verify the possibility of dynamic network analysis in detecting the locomotion state of rats. We found that the functional connectivity level was higher in the preparation phase compared to the walking phase. In addition, the cortex pays more attention to the control of hind limbs with higher requirements for muscle activity. The level of functional connectivity was lower where the terrain ahead can be predicted. Functional connectivity bursts after the rat accidentally made contact with uneven terrain, while in subsequent movement, it was significantly lower than normal walking. In addition, the classification results show that using the phase-lag index of multiple gait phases as a feature can effectively detect the locomotion states of rat during walking. These results highlight the role of the cortex in the adaptation of animals to unexpected terrain and may help advance motor control studies and the design of neuroprostheses.